tbuckley/cabot-search huggingface dataset:
Incidence of Orofacial Manifestations of Juvenile Idiopathic Arthritis From Diagnosis to Adult Care Transition: A <scp>Population‐Based</scp> Cohort Study
Authors: Mia Glerup, Aikaterini Tagkli, Annelise Küseler, Anne E. Christensen, Carlalberta Verna, Anders E. Bilgrau, Sven Erik Nørholt, Troels Herlin, Thomas K. Pedersen, Peter Stoustrup
Journal: Arthritis & Rheumatology (2023)

To estimate the cumulative incidences of orofacial conditions related to temporomandibular joint (TMJ) juvenile idiopathic arthritis (JIA) between diagnosis in childhood to transition into adult care, and to identify features in JIA associated with TMJ involvement.A population-based cohort analysis was conducted of patients with JIA involving longitudinal data on orofacial health from 2000 to 2018. Regardless of TMJ status, the patients were referred to the Regional Specialist Craniofacial Clinic of Western Denmark for routine orofacial examinations. Data collection included information about disease-specific background characteristics, TMJ involvement, JIA-induced dentofacial deformity, and orofacial symptoms and dysfunction.A total of 613 patients were followed up with a mean clinical TMJ observation time of 4.0 years. From JIA onset to transition into adult care, the cumulative incidence of patients with JIA involvement of the TMJ was 30.1%. Furthermore, 20.6% of the cohort had developed arthritis-induced dentofacial deformity. A substantial proportion of the cohort experienced several events with orofacial symptoms (23.5%) and dentofacial dysfunction (52%). Young age at diagnosis (<9 years), female gender, and antinuclear antibody positivity were significantly associated with TMJ involvement.Orofacial signs and symptoms were frequent findings in children and adolescents with JIA. TMJ involvement was seen in 30.1% of the cohort; and 20.6% of the total cohort developed JIA-related dentofacial deformity before transition into adult care. This is the first population-based study in the era of available biologic treatments to document these frequent orofacial complications in children with JIA.
Targeting RNA N6-methyladenosine to synergize with immune checkpoint therapy
Authors: Xianyong Zhou, Chen Li, Tong Chen, Wenhao Li, Xiaolong Wang, Qifeng Yang
Journal: Molecular Cancer (2023)

Abstract Cancer immunotherapy, especially immune checkpoint therapy, has revolutionized therapeutic options by reactivating the host immune system. However, the efficacy varies, and only a small portion of patients develop sustained antitumor responses. Hence, illustrating novel strategies that improve the clinical outcome of immune checkpoint therapy is urgently needed. N6-methyladenosine (m 6 A) has been proved to be an efficient and dynamic posttranscriptional modification process. It is involved in numerous RNA processing, such as splicing, trafficking, translation and degradation. Compelling evidence emphasizes the paramount role of m 6 A modification in the regulation of immune response. These findings may provide a foundation for the rational combination of targeting m 6 A modification and immune checkpoints in cancer treatment. In the present review, we summarize the current landscape of m 6 A modification in RNA biology, and highlight the latest findings on the complex mechanisms by which m 6 A modification governs immune checkpoint molecules. Furthermore, given the critical role of m 6 A modification in antitumor immunity, we discuss the clinical significance of targeting m 6 A modification to improve the efficacy of immune checkpoint therapy for cancer control.
Unusual PDGFRB fusion reveals novel mechanism of kinase activation in Ph-like B-ALL
Authors: Teresa Sadras, Fatimah B. Jalud, Hansen J. Kosasih, Christopher R. Horne, Lauren M. Brown, Sam El-Kamand, Charles E. de Bock, Lachlan McAloney, Ashley P. Ng, Nadia M. Davidson, Louise E. A. Ludlow, Alicia Oshlack, Mark J. Cowley, Seong L. Khaw, James M. Murphy, Paul G. Ekert
Journal: Leukemia (2023)
<i>Salmonella</i> effector SopF regulates PANoptosis of intestinal epithelial cells to aggravate systemic infection
Authors: Haibo Yuan, Liting Zhou, Yilin Chen, Jiayi You, Hongye Hu, Yuanyuan Li, Rui Huang, Shuyan Wu
Journal: Gut Microbes (2023)

SopF, a newly discovered effector secreted by Salmonella pathogenicity island-1 type III secretion system (T3SS1), was reported to target phosphoinositide on host cell membrane and aggravate systemic infection, while its functional relevance and underlying mechanisms have yet to be elucidated. PANoptosis (pyroptosis, apoptosis, and necroptosis) of intestinal epithelial cells (IECs) has been characterized as a pivotal host defense to limit the dissemination of foodborne pathogens, whereas the effect of SopF on IECs PANoptosis induced by Salmonella is rather limited. Here, we show that SopF can attenuate intestinal inflammation and suppress IECs expulsion to promote bacterial dissemination in mice infected with Salmonella enterica serovar Typhimurium (S. Typhimurium). We revealed that SopF could activate phosphoinositide-dependent protein kinase-1 (PDK1) to phosphorylate p90 ribosomal S6 kinase (RSK) which down-regulated Caspase-8 activation. Caspase-8 inactivated by SopF resulted in inhibition of pyroptosis and apoptosis, but promotion of necroptosis. The administration of both AR-12 (PDK1 inhibitor) and BI-D1870 (RSK inhibitor) potentially overcame Caspase-8 blockade and subverted PANoptosis challenged by SopF. Collectively, these findings demonstrate that this virulence strategy elicited by SopF aggregates systemic infection via modulating IEC PANoptosis through PDK1-RSK signaling, which throws light on novel functions of bacterial effectors, as well as a mechanism employed by pathogens to counteract host immune defense.
Inulin increases the beneficial effects of rhubarb supplementation on high-fat high-sugar diet-induced metabolic disorders in mice: impact on energy expenditure, brown adipose tissue activity, and microbiota
Authors: Marion Régnier, Matthias Van Hul, Martin Roumain, Adrien Paquot, Alice de Wouters d’Oplinter, Francesco Suriano, Amandine Everard, Nathalie M. Delzenne, Giulio G. Muccioli, Patrice D. Cani
Journal: Gut Microbes (2023)

Consumption of prebiotics and plant-based compounds have many beneficial health effects through modulation of gut microbiota composition and are considered as promising nutritional strategy for the treatment of metabolic diseases. In the present study, we assessed the separated and combined effects of inulin and rhubarb on diet-induced metabolic disease in mice. We showed that supplementation with both inulin and rhubarb abolished the total body and fat mass gain upon high-fat and high-sucrose diet (HFHS) as well as several obesity-associated metabolic disorders. These effects were associated with increased energy expenditure, lower whitening of the brown adipose tissue, higher mitochondria activity and increased expression of lipolytic markers in white adipose tissue. Despite modifications of intestinal gut microbiota and bile acid compositions by inulin or rhubarb alone, combination of both inulin and rhubarb had minor additional impact on these parameters. However, the combination of inulin and rhubarb increased the expression of several antimicrobial peptides and higher goblet cell numbers, thereby suggesting a reinforcement of the gut barrier. Together, these results suggest that the combination of inulin and rhubarb in mice potentiates beneficial effects of separated rhubarb and inulin on HFHS-related metabolic disease and could be considered as nutritional strategy for the prevention and treatment of obesity and related pathologies.
Risk of Venous Thromboembolism With Gout Flares
Authors: Edoardo Cipolletta, Laila J. Tata, Georgina Nakafero, Anthony J. Avery, Mamas A. Mamas, Abhishek Abhishek
Journal: Arthritis & Rheumatology (2023)

Objective Previous studies demonstrated that the risk of venous thromboembolism (VTE) is increased in patients with gout, but not whether there was a temporal association between gout flare and VTE. This study was undertaken to evaluate potential temporal associations between gout flare and VTE. Methods Data were obtained from electronic primary‐care records from the UK's Clinical Practice Research Datalink, which links data from hospitalization and mortality registers. Using self‐controlled case series analysis adjusted for season and age, we evaluated the temporal association between gout flare and VTE. The 90 days after primary‐care consultation or hospitalization for gout flare was designated the exposed period. This was divided into three 30‐day intervals. The baseline period was up to 2 years before the start of and up to 2 years after the end of the exposed period. The association between gout flare and VTE was measured using adjusted incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs). Results In total, 314 patients met the inclusion criteria (age ≥18 years, incident gout, no presence of VTE or use of a primary‐care anticoagulant prescription before the start of the pre‐exposure period). Among the 314 patients, VTE incidence was significantly higher in the exposed period than in the baseline period (adjusted IRR 1.83, 95% CI 1.30–2.59). The adjusted IRR of VTE during the first 30 days after gout flare was 2.31 (95% CI 1.39–3.82) relative to the baseline period. No increase in the adjusted IRRs was observed in days 31–60 (adjusted IRR 1.49, 95% CI 0.79–2.81) and days 61–90 (adjusted IRR 1.67, 95% CI 0.91–3.06) relative to baseline. Results were consistent across sensitivity analyses. Conclusion Among patients with gout, there was a transient increase in the rate of VTE within 30 days after primary‐care consultation or hospitalization for gout flare.
Liquid biopsy at the frontier in renal cell carcinoma: recent analysis of techniques and clinical application
Authors: Mingyang Li, Lei Li, Jianyi Zheng, Zeyu Li, Shijie Li, Kefeng Wang, Xiaonan Chen
Journal: Molecular Cancer (2023)

Abstract Renal cell carcinoma (RCC) is a major pathological type of kidney cancer and is one of the most common malignancies worldwide. The unremarkable symptoms of early stages, proneness to postoperative metastasis or recurrence, and low sensitivity to radiotherapy and chemotherapy pose a challenge for the diagnosis and treatment of RCC. Liquid biopsy is an emerging test that measures patient biomarkers, including circulating tumor cells, cell-free DNA/cell-free tumor DNA, cell-free RNA, exosomes, and tumor-derived metabolites and proteins. Owing to its non-invasiveness, liquid biopsy enables continuous and real-time collection of patient information for diagnosis, prognostic assessment, treatment monitoring, and response evaluation. Therefore, the selection of appropriate biomarkers for liquid biopsy is crucial for identifying high-risk patients, developing personalized therapeutic plans, and practicing precision medicine. In recent years, owing to the rapid development and iteration of extraction and analysis technologies, liquid biopsy has emerged as a low cost, high efficiency, and high accuracy clinical detection method. Here, we comprehensively review liquid biopsy components and their clinical applications over the past 5 years. Additionally, we discuss its limitations and predict its future prospects.
FixItFelix: improving genomic analysis by fixing reference errors
Authors: Sairam Behera, Jonathon LeFaive, Peter Orchard, Medhat Mahmoud, Luis F. Paulin, Jesse Farek, Daniela C. Soto, Stephen C. J. Parker, Albert V. Smith, Megan Y. Dennis, Justin M. Zook, Fritz J. Sedlazeck
Journal: Genome biology (2023)

Abstract The current version of the human reference genome, GRCh38, contains a number of errors including 1.2 Mbp of falsely duplicated and 8.04 Mbp of collapsed regions. These errors impact the variant calling of 33 protein-coding genes, including 12 with medical relevance. Here, we present FixItFelix, an efficient remapping approach, together with a modified version of the GRCh38 reference genome that improves the subsequent analysis across these genes within minutes for an existing alignment file while maintaining the same coordinates. We showcase these improvements over multi-ethnic control samples, demonstrating improvements for population variant calling as well as eQTL studies.
Proteomic and transcriptomic screening demonstrates increased mast cell–derived CCL23 in systemic mastocytosis
Authors: Stina Söderlund, Daryl Boey, Wouter van Midden, Matilda Kjellander, Kajsa Ax, Hong Qian, Joakim S. Dahlin, Johanna Ungerstedt
Journal: Journal of Allergy and Clinical Immunology (2023)
Sequential delivery of PD-1/PD-L1 blockade peptide and IDO inhibitor for immunosuppressive microenvironment remodeling via an MMP-2 responsive dual-targeting liposome
Authors: Chuan Hu, Yujun Song, Yiwei Zhang, Siqin He, Xueying Liu, Xiaotong Yang, Tao Gong, Yuan Huang, Huile Gao
Journal: Acta Pharmaceutica Sinica B (2023)

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.
Regulating the microenvironment with nanomaterials: Potential strategies to ameliorate COVID-19
Authors: Zhicheng Liu, Zhuolei Han, Xin Jin, Jusung An, Jaewon Kim, Wenting Chen, Jong Seung Kim, Ji Zheng, Jun Deng
Journal: Acta Pharmaceutica Sinica B (2023)

COVID-19, caused by SARS-CoV-2, has resulted in serious economic and health burdens. Current treatments remain inadequate to extinguish the epidemic, and efficient therapeutic approaches for COVID-19 are urgently being sought. Interestingly, accumulating evidence suggests that microenvironmental disorder plays an important role in the progression of COVID-19 in patients. In addition, recent advances in nanomaterial technologies provide promising opportunities for alleviating the altered homeostasis induced by a viral infection, providing new insight into COVID-19 treatment. Most literature reviews focus only on certain aspects of microenvironment alterations and fail to provide a comprehensive overview of the changes in homeostasis in COVID-19 patients. To fill this gap, this review systematically discusses alterations of homeostasis in COVID-19 patients and potential mechanisms. Next, advances in nanotechnology-based strategies for promoting homeostasis restoration are summarized. Finally, we discuss the challenges and prospects of using nanomaterials for COVID-19 management. This review provides a new strategy and insights into treating COVID-19 and other diseases associated with microenvironment disorders.
Full-field Scotopic Threshold Improvement after Voretigene Neparvovec-rzyl Treatment Correlates with Chorioretinal Atrophy
Authors: Katarina Stingl, Krunoslav Stingl, Hillary Schwartz, Mark W. Reid, Melanie Kempf, Spyridon Dimopoulos, Friederike Kortuem, Mark S. Borchert, Thomas C. Lee, Aaron Nagiel
Journal: Ophthalmology (2023)
MRI-AST (MAST) Score Accurately Predicts Major Adverse Liver Outcome, Hepatocellular Carcinoma, Liver Transplant, and Liver-Related Death
Authors: Emily Truong, Jeffrey A Gornbein, Ju Dong Yang, Nabil Noureddin, Stephen A Harrison, Naim Alkhouri, Mazen Noureddin
Journal: Clinical Gastroenterology and Hepatology (2023)
Low-density lipoprotein particles carrying proinflammatory proteins with altered aggregation pattern detected in COVID-19 patients 3 months after hospitalization
Authors: Thor Ueland, Lauri A.O. Äikäs, Tuva B. Dahl, Ida Gregersen, Maria Belland Olsen, Annika Michelsen, Ylva Schanke, Minna Holopainen, Hanna Ruhanen, Sachin Singh, Anders Aune Tveita, Ane-Kristine Finbråten, Lars Heggelund, Marius Trøseid, Anne Ma Dyrhol-Riise, Tuula A. Nyman, Kirsten B. Holven, Katariina Öörni, Pål Aukrust, Bente Halvorsen
Journal: Journal of Infection (2023)
Clustered HCV transmission in HIV-positive MSM and the impacts of interventions for achieving microelimination
Authors: Denise Pui Chung Chan, Bonnie Chun Kwan Wong, Ka Hing Wong, Chin Man Poon, Chin Pok Chan, Danny King Fai Cheung, Ngai Sze Wong, Shui Shan Lee
Journal: Journal of Infection (2023)
Controlling antifungal activity with light: Optical regulation of fungal ergosterol biosynthetic pathway with photo-responsive CYP51 inhibitors
Authors: Zhuang Li, Na Liu, Wanzhen Yang, Jie Tu, Yahui Huang, Wei Wang, Chunquan Sheng
Journal: Acta Pharmaceutica Sinica B (2023)

Invasive fungal infections (IFIs) have been associated with high mortality, highlighting the urgent need for developing novel antifungal strategies. Herein the first light-responsive antifungal agents were designed by optical control of fungal ergosterol biosynthesis pathway with photocaged triazole lanosterol 14α-demethylase (CYP51) inhibitors. The photocaged triazoles completely shielded the CYP51 inhibition. The content of ergosterol in fungi before photoactivation and after photoactivation was 4.4% and 83.7%, respectively. Importantly, the shielded antifungal activity (MIC80 ≥ 64 μg/mL) could be efficiently recovered (MIC80 = 0.5-8 μg/mL) by light irradiation. The new chemical tools enable optical control of fungal growth arrest, morphological conversion and biofilm formation. The ability for high-precision antifungal treatment was validated by in vivo models. The light-activated compound A1 was comparable to fluconazole in prolonging survival in Galleria mellonella larvae with a median survival of 14 days and reducing fungal burden in the mouse skin infection model. Overall, this study paves the way for precise regulation of antifungal therapy with improved efficacy and safety.
Second-line FOLFOX is not the standard of care for all patients with advanced biliary tract cancer—a commentary from the Young International Society of Geriatric Oncology
Authors: G. Liposits, S.P. Arora, N.M.L. Battisti, E. Soto-Perez-de-Celis, K.P. Loh, G.R. Williams
Journal: Annals of Oncology (2023)
Targeted PERK inhibition with biomimetic nanoclusters confers preventative and interventional benefits to elastase-induced abdominal aortic aneurysms
Authors: Nisakorn Yodsanit, Takuro Shirasu, Yitao Huang, Li Yin, Zain Husain Islam, Alexander Christopher Gregg, Alessandra Marie Riccio, Runze Tang, Eric William Kent, Yuyuan Wang, Ruosen Xie, Yi Zhao, Mingzhou Ye, Jingcheng Zhu, Yi Huang, Nicholas Hoyt, Mengxue Zhang, John A. Hossack, Morgan Salmon, K. Craig Kent, Lian-Wang Guo, Shaoqin Gong, Bowen Wang
Journal: Bioactive Materials (2023)

Abdominal aortic aneurysm (AAA) is a progressive aortic dilatation, causing ∼80% mortality upon rupture. Currently, there is no approved drug therapy for AAA. Surgical repairs are invasive and risky and thus not recommended to patients with small AAAs which, however, account for ∼90% of the newly diagnosed cases. It is therefore a compelling unmet clinical need to discover effective non-invasive strategies to prevent or slow down AAA progression. We contend that the first AAA drug therapy will only arise through discoveries of both effective drug targets and innovative delivery methods. There is substantial evidence that degenerative smooth muscle cells (SMCs) orchestrate AAA pathogenesis and progression. In this study, we made an exciting finding that PERK, the endoplasmic reticulum (ER) stress Protein Kinase R-like ER Kinase, is a potent driver of SMC degeneration and hence a potential therapeutic target. Indeed, local knockdown of PERK in elastase-challenged aorta significantly attenuated AAA lesions in vivo. In parallel, we also conceived a biomimetic nanocluster (NC) design uniquely tailored to AAA-targeting drug delivery. This NC demonstrated excellent AAA homing via a platelet-derived biomembrane coating; and when loaded with a selective PERK inhibitor (PERKi, GSK2656157), the NC therapy conferred remarkable benefits in both preventing aneurysm development and halting the progression of pre-existing aneurysmal lesions in two distinct rodent models of AAA. In summary, our current study not only establishes a new intervention target for mitigating SMC degeneration and aneurysmal pathogenesis, but also provides a powerful tool to facilitate the development of effective drug therapy of AAA.
Chemically revised conducting polymers with inflammation resistance for intimate bioelectronic electrocoupling
Authors: Sihao Qian, Hsing-An Lin, Qichao Pan, Shuhua Zhang, Yunhua Zhang, Zhi Geng, Qing Wu, Yong He, Bo Zhu
Journal: Bioactive Materials (2023)

Conducting polymers offer attractive mixed ionic-electronic conductivity, tunable interfacial barrier with metal, tissue matchable softness, and versatile chemical functionalization, making them robust to bridge the gap between brain tissue and electronic circuits. This review focuses on chemically revised conducting polymers, combined with their superior and controllable electrochemical performance, to fabricate long-term bioelectronic implants, addressing chronic immune responses, weak neuron attraction, and long-term electrocommunication instability challenges. Moreover, the promising progress of zwitterionic conducting polymers in bioelectronic implants (≥4 weeks stable implantation) is highlighted, followed by a comment on their current evolution toward selective neural coupling and reimplantable function. Finally, a critical forward look at the future of zwitterionic conducting polymers for in vivo bioelectronic devices is provided.